There are many items across Borderlands 2 and its DLCs that can only be obtained once per playthrough or character.
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Main game
- "Basic Repeater"note Unique Dahl Pistol with... nothing to note apart from all parts being fixed is the mission reward for completing the very first main story mission, "My First Gun".
- All of Moxxi's weapons, with the exception of the "Good Touch" and the "Bad Touch" qualify. Their main feature is that they heal 2% of the damage they inflict into enemies to the user:
- "Hail"note Unique Vladof Assault Rifle with +200% critical hit damage and +80% elemental splash damage whose projectiles ascend before falling in an arc and split in two after a certain distance, obtained by completing "Bandit Slaughter: Round 5".
- "Heart Breaker"note Unique Hyperion Incendiary Shotgun with increased projectile count and rate of fire and +50% critical hit bonus that shoots in a heart-shaped pattern, obtained by delivering Moxxi's pictures to herself instead of Marcus.
- "Creamer"note Unique Torgue Rocket Launcher with increased rocket velocity whose rockets split in two after a certain distance, obtained by completing the "Creature Slaughter: Round 5" sidequest.
- "Rubi"note Unique Maliwan Pistol that has a 12% Transfusion effect when wielded., the mission reward for completing "Rakkaholics Anonymous" and giving the beer to Moxxi.
- "Chère-amie"note Unique Maliwan Sniper Rifle is the mission reward for completing the sidequest "Hyperion Slaughter: Round 5".
- "1340 Shield"note Unique Vladof Absorb-type Shield with incorporated voice module and "Shotgun 1340"note Unique Hyperion Shotgun with incorporated voice module are two mission rewards for completing the "Out of Body Experience" sidequest chain and delivering the 1340 Constructor Core to either Dr. Zed or Marcus respectively.
- "The Afterburner"note Unique Eridian relic that enhances boost capacity, boost recharge rate and boost recharge delay of vehicles, the mission reward for completing "Positive Self-Image".
- "Clan War: Wakey Wakey" rewards you with either the "Aequitas"note Unique Vladof shield that increases the Fight For Your Life time +10% for every Aequitas or Veritas equipped in your team or the "Veritas"note Unique Vladof aftermarket pistol that increases the Fight For Your Life time +10% for every Aequitas or Veritas equipped in your team and has a multiplicative critical hit bonus of +10%.
- "Triquetra"note Unique Jakobs aftermarket Shotgun with increased damage and pellet count that fires pellets in a Triquetra shape, obtained by completing the "Clan War: End of the Rainbow" sidequest.
- "Landscaper"note Unique Torgue Shotgun with reduced pellet count and fire rate and increased damage and whose shots form a square and stick to inert surfaces, the stuck rounds exploding after a certain time or after an enemy is located inside its radius, the mission reward for siding with the Hodunks at the end of "Clan War: Hodunks vs. Zafords".
- "Moxxi's Endowment"note Unique Eridian Relic that increases the amount of XP gained from killing enemies, the mission reward for completing "The Good, The Bad and The Mordecai".
- "RokSalt"note Unique Bandit Shotgun with increased reload speed, accuracy, damage and rate of fire, the mission reward for completing "Splinter Group".
- "Fuster Cluck"note Unique Bandit MIRV-style Grenade Mod whose child grenades spawn mid-air after throwing the grenade, obtained as the mission reward of "The Pretty Good Train Robbery".
- "Teapot"note Unique Dahl Corrosive Pistol that has increased accuracy, elemental damage and elemental splash effect and reduced damage, fire rate, magazine size and elemental chance, the mission reward for "You Are Cordially Invited: Tea Party".
- "Roaster"note Unique Bandit Rocket Launcher with decreased base damage but increased elemental chance, status effect damage and accuracy, the mission reward for completing "Note for Self-Person".
- "Bane"note Unique aftermarket Hyperion SMG with increased damage and magazine size, at the cost of reduced accuracy and recoil reduction rate as well as an annoying voice module and highly reduced movement speed is the mission reward for completing the sidequest chain "The Bane".
- "Deputy's Badge"note Unique Eridian Relic that increases Shotgun damage and reload speed, as well as increasing "Fight For Your Life" mode by +10% for every Deputy's Badge equipped in the team is the mission reward for completing "Showdown".
- "Trespasser"note Unique Jakobs aftermarket Sniper Rifle with reduced damage and bullet speed whose bullets pass through enemy shields, dealing direct damage to the enemy, obtained as the reward for the mission "Animal Rights".
- "Octo"note Unique Tediore Shotgun that fires pellets in a 3x3 grid pattern with the centre point missing, and with two of the points receiving two pellets. The pellets move slowly and fly in sinewave pattern while leaving yellow orange trails, the mission reward for completing "Slap Happy".
- "Deadly Bloom"note Unique Torgue Nova Shield that releases a powerful nova on depletion or entering "Fight For Your Life" mode is the mission reward for completing the "The Overlooked: This Is Just A Test" sidequest.
- "Love Thumper"note Unique Bandit Maylay-style Shield with increased recharge delay and roid bonus whose melee hits create an explosive nova when the shield is depleted, the mission reward for completing "Best Mother's Day Ever".
- "Morningstar"note Unique Hyperion Sniper Rifle with increased temporary critical hit damage for every critical hit and an unique voice module that berates the user, the mission reward for completing "Hyperion Contract #873".
- "Lucrative Opportunity"note Unique Eridian Relic that speeds up the timer in the vending machines, making the machines randomize their offerings quickly, the mission reward for delivering Moxxi's pictures to Marcus at the tail end of "Safe and Sound".
- "Buffalo"note Unique Jakobs scopeless Sniper Rifle with increased damage and slightly reduced accuracy is the mission reward for completing the "Demon Hunter" sidequest.
- "Kiss of Death"note Unique Maliwan Transfusion-type Grenade Mod that homes on a target and does damage over time until explosion, releasing healing orbs for allies, obtained by completing the "Hell Hath No Fury" sidequest.
- "Scorpio"note Unique Dahl Assault Rifle with increased fire rate and magazine size that has an increased variable burst count (5-7 when zoomed in) and whose hip-fire has a chance of firing an additional shot, obtained as the mission reward for completing "Bearer of Bad News".
- "Sloth"note Unique Dahl Sniper Rifle with increased damage but reduced bullet speed, the mission reward for turning "Rakkaholics Anonymous" to Mordecai rather than Moxxi.
- "Order"note Unique Bandit Maylay Shield that converts 25% of the damage done with melee attacks into health when the "Law" Pistol is also equipped, the mission reward for completing "BFFs".
- "Dahlminator"note Unique Dahl E-Tech Corrosive Pistol that fires slow-moving projectiles and whose shots bounce in inert surfaces and stick to an enemy until they explode, dealing corrosive area-of-effect damage, obtained as the mission reward for completing the sidequest "The Lost Treasure".
- "Evil Smasher"note Unique Torgue Assault Rifle with below average stats with a chance of the next reload significantly boosting the power of the weapon until the next reload is the mission reward for completing the sidequest "The Chosen One".
- "Fibber"note Unique Hyperion Pistol whose effects depend on the barrel it spawned with, but whose displayed stats are always fake is the mission reward for completing the sidequest "A Real Boy: Human".
- "Uncle Teddy": The mission reward is to deliver T.K. Baha's plans for a weapon. The reward is...
- "Lady Fist"note Unique aftermarket Hyperion Pistol with +800% critical hit damage, reduced bullet damage, increased accuracy and magazine size for delivering it to his niece Una at the Fyrestone Bounty Board.
- "Tidal Wave"note Unique Jakobs Shotgun that fires 13 horizontal slow moving projectiles in a wave pattern that ricochets off of surfaces once if it does not hit an enemy for delivering it to the Hyperion via the mailbox at the "Arid Nexus - Boneyard" level.
- "Stomper"note Unique Jakobs Assault Rifle with high listed critical damage, the mission reward for "Hungry Like The Skag".
Captain Scarlett and Her Pirate's Booty
- "Stinkpot"note Unique Jakobs Corrosive Assault Rifle whose contagious corrosive damage spreads to other enemies and fires grenades with no initial arc until they ricochet, a drop from non-respawnable boss No-Beard.
- All of Captain Blade's cursed weapons are unique:
- "Orphan Maker"note Unique Jakobs Shotgun with increased damage and reduced pellet count that deals 5% of the damage inflicted onto enemies to the player, the mission reward for completing "Message in a Bottle (Oasis)"
- "Manly Man Shield"note Unique Torgue Shield that gives bonus damage to explosive attacks, but makes its user take increased elemental damage from all sources, obtained for completing "Message in a Bottle (Wurmwater)".
- "Rapier"note Unique Vladof Assault Rifle that deals +200% melee damage but has reduced bullet damage, it also makes its user take increased damage from melee attacks, the mission reward for completing "Message in a Bottle (Hayter's Folly)".
- "Otto Idol"note Unique Eridian Relic that restores health for every killed enemy at the cost of reducing total "Fight For Your Life" time, obtained for completing "Message in a Bottle (The Rustyards)".
- "Midnight Star"note Unique Torgue MIRV-style Grenade Mod that has increased damage but reduced child grenade count; the child grenades fly towards their user, obtained for completing "Message in a Bottle (Magny's Lighthouse)".
- "Jolly Roger"note Unique Bandit Shotgun with increased pellet count and fixed spread pattern that forms a "Skull & Bones" pattern, obtained as the mission reward for "Just Desserts for Desert Deserters".
- "Sand Hawk"note Unique aftermarket Dahl SMG that consumes three rounds per shot and produces 8 projectiles that move in a bird-shaped pattern and become transparent after a certain distance, the mission reward for completing "Whoops!".
- "Pimpernel"note Unique Maliwan Sniper Rifle that shoots two consecutive shots: if the first hits a surface or hitbox, a second pellet moves vertically in a straight line and splits into 5 pellets moving in a star-like pattern with the card's stats and can hit a second time at 50% damage, the mission reward for completing "Don't Copy That Floppy".
- "Greed"note Unique Jakobs Incendiary Pistol whose aiming down sights don't have movement speed penalty, obtained during the main story quest "X Marks The Spot" and the sidequest "Treasure of the Sands".
Mr. Torgue's Campaign of Carnage
- "Boom Puppy"note Unique Torgue Assault Rifle with decreased fire rate and reload speed which fires a bouncy grenade with each shot, the grenade itself exploding every time it bounces until a certain amount of seconds have passed is the mission reward for completing the main story mission "Walking the Dog".
- "Kitten"note Unique Vladof Assault Rifle that fires three bullets at the cost of one ammo unit, and whose shots spread in order to form a smileying face, the spread starting tight, then lengthening then closes in again; as a Moxxi weapon it also deals Transfusion damage to the enemy, healing its user, the mission reward for completing "Everybody Wants to be Wanted".
Tiny Tina's Assault on Dragon Keep
- Moxxi's weapons exclusive to this DLC share the same trait as their main game counterparts, but add twists on their own:
- "Crit"note Unique aftermarket Maliwan Shock SMG with increased overall stats and 150% critical bonus damage which can drop when reloaded, obtained by completing the "Critical Fail" sidequest.
- "Grog Nozzle"note Unique Maliwan Slag Pistol with extremely increased Slag chance, very low damage (-80%) and highly increased (+200%) critical hit damage which fires large, slow bullets that explode three times mid-flight; heals the wielder for 65% of the damage done, obtained during the sidequest "The Beard Makes The Man".
- "Mysterious Amulet"note Unique Eridian Relic that, when equipped and feeding Eridium to Butt Stallion in "The Backburner" after completing "My Brittle Pony" in the DLC Commander Lilith and the Fight for Sanctuary, has a chance of her vomiting the "Unicornsplosion!", the mission reward for completing "The Amulet".
- "SWORDSPLOSION!"note Unique Torgue E-Tech Shotgun that consumes two ammo units per shot and fires a single sword projectile that explodes in three smaller swords which also explode on impact, obtained as the mission reward for "The Sword in the Stoner".
- "Orc"note Unique Bandit SMG with a chance to randomly activate one of six short-lived boosts on firing, reloading, swapping weapons, or opening a menu, obtained as a reward for completing "Magic Slaughter: Round 5".
Other
- The Pre-Order Bonus "Contraband Sky Rocket"note Unique Bandit Incendiary Grenade Mod with greatly increased (and level-scalable) damage and blast radius that shoots upward rockets and releases a burst of fireworks can only be obtained once per character.
